Polygenic Risk, Agent Orange Exposure, and Lymphoid Neoplasms in the Veterans Affairs Million Veteran Program

Is Agent Orange (AO) exposure associated with increased risk of developing mature lymphoid malignant neoplasms, and is there a joint association of AO exposure and polygenic risk?In this case-control study of 255 155 US veterans, both the polygenic risk score and AO exposure were associated with the development of chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma. No significant polygenic risk score × AO interaction was observed in any of these lymphoid malignant neoplasms.These findings suggest that AO exposure and polygenic risk independently contribute to lymphoma malignant neoplasm risk without evidence of interaction, pointing to distinct and potentially additive pathways.

Corresponding Author: Helen Ma, MD, Tibor Rubin Veteran Affairs Medical Center¸5901 E Seventh St, Long Beach, CA 90822 (helen.ma@va.gov).

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